The sensory structures of the mammalian inner ear are contacted by four main types of nerve fibers. Two types are afferent, carrying information from the ear to the brain, while two are efferent, carrying signals from the brain back to the ear. Remarkably little is known about why so many neuronal types are needed and what role each plays in the overall process of hearing. The long-term aims of this R01 are to better understand the complex interplay among these neurons by applying a variety of anatomical and physiological techniques to the study of animal models. Over the next five years, we concentrate on the two efferent pathways and their effects on the inner ear. One of these pathways, the medial olivocochlear (MOC) fibers to the outer hair cells, responds to sound and thus completes an acoustic reflex to the inner ear. One hypothesis about the role of this reflux is that it improves the detection of signals in noise. We propose to directly measure such "anti-masking" effects by recording auditory nerve fiber responses while reversibly blocking the MOC reflex. Our results should suggest what auditory tasks are most impaired in those individuals lacking an MOC reflex and may suggest a physiological basis for the marked deterioration in hearing ability in noise for individuals with sensorineural hearing loss. Another proposed role for the OC pathway is in protecting the inner ear from acoustic overstimulation; however, the results from different laboratories are contradictory. We propose a series of experiments to resolve these contradictions and, further, to determine whether a protective effect extends to permanent as well as temporary threshold shifts and to understand the mechanisms underlying such effects. If the OC system does play a protective role, understanding this natural "defense" mechanism may help explain why some individuals are much more susceptible to acoustic injury than others and may provide clues as to how such natural defenses could be enhanced. The function of the lateral olivocochlear (LOC) pathway, which terminates principally on auditory nerve fibers under the inner hair cells (IHCs), is completely unknown. We have preliminary results suggesting that, if the OC pathway is interrupted at birth, the normal relationship between spontaneous rate (SR) and threshold sensitivity in the auditory nerve fails to develop. We propose to determine whether these effects are due to the loss of LOC innervation. A parallel series of anatomical experiments will exploit intracellular labeling techniques to examine the morphological basis for the SR-based differences among auditory nerve fibers in the normal adult, both with respect to the nature of the lOC terminals contacting them and the structure of their synaptic specializations with the IHCs (as seen in transmission electron microscopy and freeze fracture). Explaining the mechanisms underlying the sensitivity differences among IHC afferents is key to an understanding of the control of dynamic range in the auditory periphery.